The genesis of cardiac allograft vasculopathy has been linked to nonimmunologic endothelial injury. Studies evaluating the role of nonimmunologic risk factors have thus far been limited to angiographic assessment. Intravascular ultrasound can detect cardiac allograft vasculopathy before it becomes angiographically evident. To assess the influence of nonimmunologic risk factors in the development of cardiac allograft vasculopathy, we studied 101 consecutive cardiac transplant recipients who underwent intracoronary ultrasound imaging during routine, annual coronary angiography. Based on the severity of intimal thickening, patients were divided into 2 groups: group 1 = minimal, mild, or moderate intimal thickness; and group 2 = severe intimal thickness. Cardiac transplant recipients with severe intimal thickness had higher levels of total cholesterol (267 +/- 70 vs 227 +/- 41 mg/dl, p = 0.0008), low-density lipoprotein cholesterol (187 +/- 47 vs 139 +/- 31 mg/dl, p = 0.0001), and triglycerides (237 +/- 75 vs 182 +/- 88 mg/dl, p = 0.0004), a higher percentage of weight gain (12 +/- 4% vs 8 +/- 5%, p = 0.0001), a larger body mass index (30 +/- 4 vs 25 +/- 3, p = 0.0001), and older donor age (27 +/- 5 vs 23 +/- 7 years, p = 0.005) than recipients with mild or moderate intimal thickness. Multiple regression analysis established that total cholesterol, low-density lipoprotein cholesterol, triglyceride levels, obesity indexes, donor age, and years following cardiac transplantation (p < 0.01) were independent predictors of the severity of intimal thickening, and thus the severity of cardiac allograft vasculopathy.(ABSTRACT TRUNCATED AT 250 WORDS)